This application, consisting of two projects, is a joint effort of 44 centers of the NAPRTCS and its two core laboratories of Cornell and Harvard Universities. Project I is entitled "Steroid withdrawal (SW) post- transplantation (PT)" and has 4 specific aims. We will conduct a randomized trial (ratio 2:1) of 600 primary transplant recipients to test the 1st hypothesis, that patients randomized to RAD, cyclosporine (CSA) and prednisone (P) (test arm) will have significantly less acute rejections in the first six months than the control arm of mycophenolate mofetal (MMF), CSA and P. To test the 2nd hypothesis, that test arm patients who are rejection free by histology (H) and molecular (M) studies can be weaned off P, whereas patients with a H clean biopsy but M evidence of rejection will fail SW, we will perform a protocol biopsy on all clinically rejection free test arm patients six months. PT and randomize (1:1) those who are clear to continue P or to undergo SW. We will perform RT-PCR on the protocol biopsy tissues to quantify mRNA encoding granzyme B, perforin and Fas ligand (CTL), and cytokines IL-10, TNFalpha and TGF- beta1. To test the 3rd hypothesis, that peripheral blood and urine can serve as surrogate markers for intragraft events, we will quantify gene expression for CTL and cytokines in blood and urine obtained at the time of protocol and rejection biopsies following SW. To test the 4th hypothesis, that a high TGF-beta1/low TNFalpha and low IL-10 genotype, is a surrogate marker for steroid withdrawal-permissive donor- specific hyporesponsiveness we will study the individual genotype for these cytokines in all patients in the SW trial using ARMS PCR. Project II is entitled "Pilot study of anti-CD40L mAb in repeat cadaver donor transplants," and has two specific aims. To test the 1st hypothesis, that treatment using a co-stimulatory blockade without calcineurin inhibition will enable us to achieve on-year graft survival comparable to that seen in primary transplants (85%), we will perform an open label trial using the Biogen antibody hu5c8 with steroids and MMF in 66 cadaver donor repeat transplants. To test the 2nd hypothesis, that the interruption of the CD40/CD40L pathway will result in the absence or reduced expression of CTL molecules and cytokines IL-2, IFNgamma, IL-10, IL-12 and up- regulation of IL-4 in surveillance biopsies (RB), we will perform an SB on all patients on day 12 and an RB with each episode. The biopsy tissue will be studied by PCR and by immunohistology.